During the past year I accumulated evidence on the anatomical sites where opiates exert their effects on the brain. The overall conclusion to date is that morphine conditions the central autonomic nervous system so that the organism interprets its internal system as being in homeostasis. This stabilization of the internal milieu by opiates may account for its overall pharmacological effects, namely, decreased respiration, failure to maintain body temperature and response to noxious stimuli. I found that the specific sites involved in opiate effects are localized in the medial regions of the subcortical brain. In further studies I suggested that central thermal regulatory mechanisms may be selectively affected by morphine and that withdrawal signs are due to imbalances of central temperature control. In studying the neurochemical correlates of morphine effects I noted that intracerebral microinjections of thyrotrophin-releasing hormone (TRH) in the rat produced a behavioral syndrome which mimicked some of the abstinence signs of morphine withdrawal. (TRH is a small peptide which is suspected of having extra-hypothalamic functions.) It is possible that endogenous peptides which influence neuronal membranes functions mediate the mechanisms of opiate actions on the brain. In collaboration with Drs. Horace Loh and C.H. Li of the University of California San Francisco Medical Center, we found that beta-endorphin, a 31 amino acid peptide, has potent central analgesic activity. I infused beta-endorphin into the brain of rats with osmotic minipumps and found that this peptide can cause typical morphine-like physical dependence. These results suggest that the body can carry its own narcotic-like addicting substance. BIBLIOGRAPHIC REFERENCES: E. Wei & H. Loh. Chronic, intracerebral infusion of opiates and peptides with osmotic minipumps, and the development of physical dependence. Proc. of the International Narcotics Research Club, Aberdeen, Scotland, July 19-22, 1976. E. Wei. Interaction of opiates with agents which cause withdrawal-like syndromes. Proc. of an International Symposium on "Factors Affecting Narcotics", Milan, Italy, July 13-16, 1976.